13 March 2019

Get up on the call

Doctors will be able to treat people with spinal cord injury

Olga Kolentsova, Izvestia

A drug based on two genes will help restore the patient's motor activity after spinal cord injury. The revolutionary development of Russian scientists protects neurons from death, stimulates the growth of blood vessels and new nerve fibers. The effectiveness of the drug was shown by experiments conducted on rats – a few months after the start of treatment, the animals were able to walk on previously paralyzed limbs. In order to start preclinical trials, the researchers had to solve funding problems.

Prevent scarring

Spinal cord injury resulting from an accident, accident or fall from a height often leads to loss of sensitivity and the ability to move parts of the body below the site of injury. Now only an exoskeleton and neuroprostheses can help the muscles to amplify the signal, and then provided that the connection between the spinal cord and the brain is not completely lost. Researchers from Kazan Federal University (KFU) have created a drug that allows you to successfully fight spinal cord injuries, despite the presence of factors complicating recovery.

The fact is that when the spinal cord is damaged, the body gradually builds up a scar consisting of connective tissue at the site of injury. It is necessary for a kind of fixation of the injury site, but further prevents the growth of axons, processes of nerve cells, with which communication with other cells is carried out.

The researchers were faced with the task of creating a drug that would reduce the rate of scar formation and restore nerve tissue.

Ampoule with DNA

Researchers from the Institute of Fundamental Medicine and Biology of KFU have created such a drug, taking two genes (VEGF and FGF2) as its basis. The first gene normalizes blood supply in neurotrauma, supports the survival of neurons, stimulates neurogenesis, the growth of new vessels and axons. The second gene is a growth factor, has a pronounced neurotrophic effect – supports cell survival in the area of damage, promotes the development of nerve fibers. The resulting drug also contains regulatory elements that control the work of these genes.

– There are no changes in human DNA, both of these genes are already present in the human body, – explained Albert Rizvanov, head of the Laboratory of Gene and Cell Technologies at the Institute of Fundamental Medicine and Biology of KFU. – We simply insert additional copies of active genes into the body, with the help of several microinjections into the spinal cord above and below the injury. Thus, we modify part of the nerve cells (but do not "interfere" with their nucleus) and "program" them for enhanced growth and recovery.

The drug was tested on animals as follows. In order to simulate spinal cord injury, the subjects' spine was opened and a strictly defined force was struck on it with a special hammer. After the operation, the animals lost the sensitivity of the hind limbs and the ability to move them. During the whole experiment, the animals were carefully cared for, helping to cope with hygiene and food intake.

After the injury, the scientists moved on to treatment. The experimental group of animals was injected with a gene drug, and the control group was allowed to recover without outside intervention.

Move your paws

In the rats of the control group, two months after the injury, a partial recovery of motor functions was observed – the animals bent their paws in one or two joints. However, the rodents could not fully move, hold their body weight and coordinate their movements. The rats in the experimental group during the same period began to confidently stand on their paws, walk, controlling the movements of the fore and hind limbs.

– In addition to the use of a gene drug, we are conducting research on the effectiveness of treating spinal cord injuries using mesenchymal stem cells, – said Yana Mukhamedshina, senior researcher at the Laboratory of Gene and Cell Technologies at the Institute of Fundamental Medicine and Biology of KFU. – The results of both studies are encouraging and show that we can effectively restore the injured spinal cord and its functions in large animals, in particular pigs, and later in humans.

In the future, scientists plan to combine these techniques for the treatment of brain injuries and therapy of neurodegenerative diseases.

Despite the fact that the genes in the composition of the drug are already present in the human body, there is still an element of risk and it is impossible to predict, says Andrey Zamyatnin, director of the Institute of Molecular Medicine of the Sechenov University Biomedical Science and Technology Park.

– As part of the genetic structure that is used, there are parts (regulatory elements) that are absent in the human body, – he explained. – Their effect on the body is absolutely unpredictable. Therefore, to prove the safety of the drug, it is necessary to conduct clinical trials.

Scientists are ready to start preclinical trials within a year if they decide on funding.

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